Catheters are presently utilized in a great variety of medical procedures where they provide a great benefit to patients and medical practitioners. Unfortunately, conventional catheters are capable of being contaminated with microorganisms. Catheter-related infections are thought to arise by several different mechanisms. Contamination of the catheter hub and subsequent colonization of catheters by microbes as well as formation of a bacterial biofilm on the external and internal surfaces are thought to be the major routes for catheter related infections. Many catheter related blood stream infections (CRBSI) are derived from intraluminal contaminants. To address this problem, catheter lumens can be locked with an antimicrobial solution. For the purposes of this disclosure, the term, “locked” refers to filling the catheter lumen with a solution that is allowed to dwell or remain in place for at least a minute. Catheter lock solutions containing salts of citrate, ethanol, ethylenediaminetetraacetic acid (EDTA), antibiotics and methylene blue are generally known. See: 1) Garland J. S., Alex C. P., Henrickson K. J., McAuliffe T. L., and Maki D. G. (2005) A vancomycin-heparin lock solution for prevention of nosocomial bloodstream infection in critically ill neonates with peripherally inserted central venous catheters: a prospective, randomized trial. Pediatrics 116: e198-205; 2) Weijmer M. C., Van den Dorpel M. A., Van de Ven P. J. G. (2005) Randomized, Clinical Trial Comparison of Trisodium Citrate 30% and Heparin as Catheter-Locking Solution in Hemodialysis Patients. J Am Soc Nephrol 16: 2769-2777; 3) Ash S. R. (2005) Method of enhancing catheter patency using a citrate salt catheter lock solution. United States Patent Application US20050215978A1; 4) Ash S. R. (2000) Method of enhancing catheter patency using a citrate salt catheter lock solution. International Patent WO 00/10385 A1; and 5) Opilla M. T., Kirby D. F., and Edmond M. B. (2007) Use of ethanol lock therapy to reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients. JPEN J Parenter Enteral Nutr. 31: 302-305. Most of these conventional lock solutions have shown benefit in reduction of CRBSI when these solutions were allowed to dwell for extended periods, e.g., while the lumen was not in use.
The composition of a bacteriostatic lock solution containing glycerol and saline is known. The glycerol lock can be utilized as a preventive lock for long term application as it causes bacterial stasis on short term exposure but only killing of bacteria on extended exposure. The present invention relates to the composition of an antimicrobial catheter lock solution which is fast acting (e.g., less than 1 hour) and therefore can be used as a salvage lock when infection symptoms are present and a contaminated catheter is suspected. A recent clinical trial on 50% ethanol lock solution where locking was performed from 1-3 hours showed no reduction in infection relative to heparin locking (Crnich C. J., Duster M., Jones A., and Maki D. G. Prospective Randomized Double-Blind Trial of an Ethanol Lock for Prevention of CLABSI. Proceedings 49th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, Calif. Sep. 12-16, 2009.). Thus, there still remains a need for a safe lock that can eradicate bacteria and preformed biofilms rapidly.
Accordingly, it is desirable to provide a catheter lock solution having antimicrobial properties that is capable of overcoming the disadvantages described herein at least to some extent.